LHRH neurons, critical for reproduction, are derived from the nasal placode and migrate into the brain where they become integral members of the hypothalamic-pituitary-gonadal axis. We study mechanism(s) underlying LHRH neuronal differentiation, migration and axonal targeting in normal/transgenic animals, and nasal explants. Intrinsic and trans-synaptic regulation of LHRH gene expression, peptide synthesis and secretion in LHRH neurons are studied using nasal explants, cell lines and normal and transgenic animals. Previous work in our lab 1) showed that outgrowth of olfactory axons and migration of LHRH neurons occur in isolated olfactory pit tissue, 2) revealed olfactory axon 'guidance cues' localized to midline nasal cartilagenous tissue, 3) showed GABA was an important factor in the migration of LHRH neurons in nasal regions and 4) identified a novel gene termed NELF which we hypothesize acts via a homophilic interaction to influence LHRH neuronal migration on olfactory axons. Over the past year, we have continued our work characterizing the expression pattern of NELF during development. NELF is primarily limited to PNS and CNS tissues, being highly expressed in the thalamus both prenatally and postnatally. In addition, we have shown that maturation of LHRH neurons in nasal explants parallels LHRH neurons in vivo, with respect to peptide synthesis and processing and that devoid of CNS tissues LHRH neurons exhibit synchronous neuronal activity. Future studies are directed at the molecules and cues important for development of the olfactory and LHRH neuronal systems as well as the mechanisms regulating LHRH neuronal activity. Specific studies in progress focused on: 1) isolation of midline cues which influence olfactory axon outgrowth; 2) the role of NELF and other molecules in LHRH migration, 3) identifying pacemaker molecules in LHRH neurons that participate in establishment/maintenance of rhythmic activity 4) genes differentially expressed in LHRH neurons as a function of GABAergic stimulation and 5) expression of receptors and channels in LHRH neurons as a function of development.